Mechanisms of nitric oxide‐induced apoptosis in bovine chromaffin cells: Role of mitochondria and apoptotic proteins

Abstract

The aim of this work was to establish the possible involvement of mitochondria in the apoptotic event triggered by nitric oxide (NO) in chromaffin cells. Using bovine chromaffin cells in primary culture and several NO donors (SNP, SNAP, and GSNO) at apoptotic concentrations (50 microM-1 mM), we have shown that NO induces a time-dependent decrease in the mitochondrial transmembrane potential (DeltaPsi(m)), which correlates with the appearance of hypodiploid cells. Disruption in DeltaPsi(m) is followed by cytochrome c release to the cytosol, which in turn precedes caspase 3 activation. In this mechanism participates the Bcl-2 protein family, because NO donors downregulate the expression of anti-apoptotic members of the family such as Bcl-2 and Bcl-XL, and increase the expression of pro-apoptotic members, Bax and Bcl-Xs, inductors of cytochrome c release to cytosol. Different cell signaling pathways seem to regulate Bax induction and Bcl-2 inhibition because decreased Bcl-2 levels are detected later than enhanced Bax expression. The tumour suppressor protein p53 is also upregulated in a very early phase (30 min) of the NO-induced apoptosis and may be responsible for the further induction of Bax expression. Finally, the translocation of NF-kappaB to the nucleus seems to be another early event in NO-induced apoptosis and it may be involved in the regulation of p53 expression. These results support strongly the participation of mitochondrial mechanisms in NO-induced apoptosis in chromaffin cells and suggest that these cells may be good models for the investigation of molecular basis of neurodegeneration and neuroprotection.

Linoleic Acid Derivative DCP-LA Protects Neurons from Oxidative Stress-Induced Apoptosis by Inhibiting Caspase-3/-9 Activation

“…SNP disrupts mitochondrial membrane potentials, which triggers cytochrome c release from the mitochondria [16]. The ensuing events include activation of caspase-9 and the downstream effector caspase caspase-3, to induce apoptosis.…”

Cytokine Interactions with Adrenal Medullary Chromaffin Cells

“…IFN-c was shown to activate the STAT3 signalling pathway to mediate suppression of nNOS activity. The resultant fall in nitric oxide (NO) levels stimulated a nuclear factor jB (NFjB)-mediated increase in iNOS expression causing a net rise in cellular NO which had previously been shown to induce apoptosis in these cells (Perez-Rodriguez et al 2009;Perez-Rodriguez et al 2007). In addition to describing the IFN-c pathway in chromaffin cells, this article concludes with the potentially significant proposal that this IFN-c-induced apoptosis may serve as a useful model for studying apoptotic mechanism in the CNS.…”

Role of SIRT1/PGC-1α in mitochondrial oxidative stress in autistic spectrum disorder

“…During apoptosis a variety of cellular signals from the mitochondria, membrane, and cytosol are activated by stimuli 17. Additionally, mitochondria may sense these cellular signals and then lead to cell apoptosis by releasing proapoptotic factors into the cytosol, such as Smac-DIABLO and cytochrome c (cyto c ) 18. Moreover, the apoptosis induced by mitochondrial oxidative stress has been proposed to be associated with ASD 19…”